16-3089389-C-T

Variant names:

• chr16-3089389-C-T
• rs1444086852
• NM_032805.3:c.2045G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032805.3(ZSCAN10):​c.2045G>A​(p.Arg682His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZSCAN10 NM_032805.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.459
• Publications: 0 publications found

Genes affected

ZSCAN10 (HGNC:12997): (zinc finger and SCAN domain containing 10) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated and regulation of transcription by RNA polymerase II. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZSCAN10 Gene-Disease associations (from GenCC):

• otofacial neurodevelopmental syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29191884).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032805.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN10	NM_032805.3	MANE Select	c.2045G>A	p.Arg682His	missense	Exon 6 of 6	NP_116194.2	Q96SZ4-1
	ZSCAN10	NM_001282416.2		c.1634G>A	p.Arg545His	missense	Exon 5 of 5	NP_001269345.1	Q96SZ4-3
	ZSCAN10	NM_001365272.1		c.1499G>A	p.Arg500His	missense	Exon 5 of 5	NP_001352201.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN10	ENST00000576985.6	TSL:5 MANE Select	c.2045G>A	p.Arg682His	missense	Exon 6 of 6	ENSP00000458879.2	I3L1J3
	ZSCAN10	ENST00000252463.6	TSL:1	c.1880G>A	p.Arg627His	missense	Exon 5 of 5	ENSP00000252463.2	A0ABB0GZV6
	ZSCAN10	ENST00000538082.5	TSL:4	c.1634G>A	p.Arg545His	missense	Exon 5 of 5	ENSP00000440047.2	Q96SZ4-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450968 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 722292

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33108

American (AMR) AF: 0.0000226 AC: 1 AN: 44282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25938

East Asian (EAS) AF: 0.00 AC: 0 AN: 39484

South Asian (SAS) AF: 0.00 AC: 0 AN: 86054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110434

Other (OTH) AF: 0.00 AC: 0 AN: 60150

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0448430), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.46
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.53		Loss of methylation at R627 (P = 0.0188)
MVP		0.49
MPC		2.1
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.59
gMVP		0.40
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1444086852; hg19: chr16-3139390; COSMIC: COSV52966788; COSMIC: COSV52966788;